Abstract：
:The function of the 90-kDa heat shock protein (Hsp90) is essential for the regulation of a myriad of signal transduction cascades that control all facets of a cell's physiology. Akt (PKB) is an Hsp90-dependent serine-threonine kinase that plays critical roles in the regulation of muscle cell physiology, including roles in the regulation of muscle differentiation and anti-apoptotic responses that modulate cell survival. In this report, we have examined the role of Hsp90 in regulating the activity of Akt in differentiating C2C12 myoblasts. While long-term treatment of differentiating C2C12 cells with the Hsp90 inhibitor geldanamycin led to the depletion of cellular Akt levels, pulse-chase analysis indicated that geldanamycin primarily enhanced the turnover rate of newly synthesized Akt. Hsp90 maintained an interaction with mature Akt, while Cdc37, Hsp90's kinase-specific co-chaperone, was lost from the chaperone complex upon Akt maturation. Geldanamycin partially disrupted the interaction of Cdc37 with Akt, but had a much less significant effect on the interaction of Hsp90 with Akt. Surprisingly, short-term treatment of differentiating C2C12 with geldanamycin increased the phosphorylation of Akt on Ser473, an effect mimicked by treatment of C2C12 cells with okadaic acid or the Hsp90 inhibitor novobiocin. Furthermore, Akt was found to interact directly with catalytic subunit of protein phosphatase 2A (PP2Ac) in C2C12 cells, and this interaction was not disrupted by geldanamycin. Thus, our findings indicate that Hsp90 functions to balance the phosphorylation state of Akt by modulating the ability of Akt to be dephosphorylated by PP2Ac during C2C12 myoblast differentiation.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Yun BG,Matts RLdoi
10.1016/j.cellsig.2005.03.006subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1477-85issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(05)00057-4journal_volume
17pub_type
杂志文章abstract：:A tight control of the machineries regulating membrane bending and actin dynamics is very important for the generation of membrane protrusions, which are crucial for cell migration and invasion. Protein/protein and protein/phosphoinositides complexes assemble and disassemble to coordinate these mechanisms, the scaffol...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109692
更新日期：2020-09-01 00:00:00
abstract：:TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and metastasis. However, the mechanisms by which TMPRSS4 contributes to invasion are not fully und...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.08.002
更新日期：2014-02-01 00:00:00
abstract：:We previously showed that an increase of cellular Bcl-xL mediates acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and knockdown of Bcl-xL expression greatly sensitized TRAIL-induced cytotoxicity. Here, we show that Daxx downregulation increases the anti-tumorigenic activity throu...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.02.028
更新日期：2015-06-01 00:00:00
abstract：:Cytidine monophosphate kinase (CMPK), a member of the nucleoside monophosphate kinase family, plays an important role in the biosynthesis of nucleoside metabolism, DNA repair and tumour development. In this study, we demonstrated for the first time that CMPK was overexpressed in human ovarian epithelial borderline and...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2017.04.009
更新日期：2017-07-01 00:00:00
abstract：:T-2 toxin, a major compound of trichothecenes, inhibits protein synthesis and induces inflammation and cell apoptosis through the activation of MAPK pathway. The JAK/STAT pathway has recently been shown to be downstream targets of trichothecenes. However, whether there is any crosstalk between JNK and JAK/STAT pathway...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.09.013
更新日期：2014-12-01 00:00:00
abstract：:The kidney is one of the fastest-aging organs, and renal senescence has become a major disease affecting human health. Renal cellular senescence is regulated by the joint action of multiple signal transduction pathways. The previous study by our research group found that the Janus kinase 2 (JAK2)/signal transducer and...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.10.021
更新日期：2019-01-01 00:00:00
abstract：:Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.09.030
更新日期：2010-01-01 00:00:00
abstract：:Mitogen-activated protein kinases (MAPKs) define a specific group of eukaryotic protein kinases which regulate a number of cellular functions by transducing extracellular signals to intracellular responses. Unlike other protein kinases, catalytic activation of MAPKs by MAPKKs depends on dual phosphorylation at two tyr...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.09.017
更新日期：2015-12-01 00:00:00
abstract：:We previously showed that activated peroxisome proliferator-activated receptor (PPAR)β/δ can protect pancreatic β cells against lipotoxic apoptosis. However, the molecular mechanism remained unclear. Glucagon-like peptide-1 receptor (GLP-1R) has been reported to exhibit a protective effect against lipotoxic apoptosis ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.11.019
更新日期：2014-02-01 00:00:00
abstract：:We demonstrate the difference between the follistatin isoforms (FS-288 and FS-315), two activin-binding proteins, in the neutralizing activity for activin signalling. Transcriptional reporter assay using 3TP-Lux, an activin-responsive reporter construct, showed that the inhibitory effect of FS-288 on activin-induced t...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00099-1
更新日期：2000-08-01 00:00:00
abstract：:The Wnt signalling pathway is conserved in various species from worms to mammals, and plays important roles in development, cellular proliferation, and differentiation. The molecular mechanisms by which the Wnt signal regulates cellular functions are becoming increasingly well understood. Wnt stabilizes cytoplasmic be...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(99)00054-6
更新日期：1999-11-01 00:00:00
abstract：:We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(03)00014-7
更新日期：2003-08-01 00:00:00
abstract：:Beyond its key role in the control of energy metabolism, insulin is also an important regulator of cell division and neoplasia. However, the molecular events involved in insulin-driven cell proliferation are not fully elucidated. Here, we show that the ubiquitin ligase Chfr, a checkpoint protein involved in G2/M trans...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.01.003
更新日期：2015-04-01 00:00:00
abstract：:When oxygen sensing cells are excited by hypoxia, background K+ currents are inhibited. TASK-1, which is commonly expressed in oxygen sensing cells and makes a background K+ current, is inactivated by hypoxia. Thus TASK-1 is a candidate molecule responsible for hypoxic excitation. However, TASK-1 per se cannot sense o...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.05.025
更新日期：2006-04-01 00:00:00
abstract：:Calcineurin (CnA) is an important signalling molecule in skeletal muscle, in the promotion of differentiation, slow-fibre phenotype and possibly fibre hypertrophy. We found that stable expression of constitutively active CnA in muscle C2C12 cells strongly activated NF-kappaB, a key mediator of muscle wasting. NF-kappa...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(02)00120-1
更新日期：2003-05-01 00:00:00
abstract：:IFN-gamma and TNF-alpha are major proinflammatory cytokines implicated in islet beta-cell destruction, which results in type-1 diabetes; however, the underlying mechanism is not clear. Using pancreatic beta-cell line MIN6N8 cells, co-treatment with TNF-alpha and IFN-gamma, but neither cytokine alone, synergistically i...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.03.020
更新日期：2005-12-01 00:00:00
abstract：:Interleukin-6-type cytokine receptors are expressed in polarized cells such as hepatocytes and intestinal cells. For the interleukin-6-receptor gp80 and its signal transducer gp130, a preferential basolateral localization was demonstrated in Madin-Darby canine kidney (MDCK) cells and two basolateral sorting signals we...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.09.006
更新日期：2006-08-01 00:00:00
abstract：:Epac1 is a cAMP-stimulated guanine exchange factor that activates Rap1. The protein product of the T cell leukemia 1 (TCL1) proto-oncogene binds to Akt enhancing its kinase activity. TCL1 and Epac promote cellular proliferation because of their activating effects on Akt. Employing macrophages, we have studied the mech...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2007.10.008
更新日期：2008-01-01 00:00:00
abstract：:Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we repor...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.01.015
更新日期：2006-10-01 00:00:00
abstract：:Signaling co-receptors are diverse, multifunctional components of most major signaling pathways, with roles in mediating and regulating signaling in both physiological and pathophysiological circumstances. Many of these signaling co-receptors, including CD44, glypicans, neuropilins, syndecans and TssRIII/betaglycan ar...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2009.05.001
更新日期：2009-11-01 00:00:00
abstract：:Endogenous reactive oxygen species (ROS) control is important for the maintenance of self-renewal of embryonic stem (ES) cells. Although miRNAs have been found to be critically involved in the regulation of the self-renewal, whether miRNAs can regulate the signaling axis to control ROS in ES cells is unclear. Here we ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.03.010
更新日期：2014-07-01 00:00:00
abstract：:Octimibate and related nonprostanoid prostacyclin mimetics are partial agonists displaying highly tissue-specific responses. Octimibate demonstrated considerably greater efficacy for stimulation of adenylyl cyclase activity in Chinese hamster ovary cells transiently expressing mouse prostacyclin receptors (mIP-CHO cel...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(01)00210-8
更新日期：2001-11-01 00:00:00
abstract：:Wnt3a activates proliferation of fibroblasts cells via activation of both extracellular signal-regulated kinase (ERK) and Wnt/beta-catenin signaling pathways. In this study, we show that the phosphatidyl inositol 3 kinases (PI3K)-Akt pathway is also involved in the Wnt3a-induced proliferation. Akt was activated within...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.08.008
更新日期：2007-03-01 00:00:00
abstract：:How might a microbial cell that is entirely metabolically dormant - and which has the ability to remain so for extended periods of time - irreversibly commit itself to resuming vegetative growth within seconds of being exposed to certain amino acids or sugars? That this process takes place in the absence of any detect...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109729
更新日期：2020-10-01 00:00:00
abstract：:Induction of apoptosis in Hep3B hepatoma cells by transforming growth factor beta 1 (TGF-beta 1) was accompanied by the activation of interleukin-1-beta-converting-enzyme-like proteases, which have recently been renamed as caspases. The caspase inhibitor ZVAD-FMK, which has a broader specificity for caspase family pro...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(97)00189-7
更新日期：1998-07-01 00:00:00
abstract：:The p75 neurotrophin receptor (p75(NTR)) plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation and proliferation. To evaluate the influence of p75(NTR) in breast cancer development, we have established and characterized breast cancer cells which stably overe...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.07.014
更新日期：2010-12-01 00:00:00
abstract：:We analyse the role of the G proteins in regulating collagen gene expression by measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in basal conditions and after stimulating or inhibiting the major intracellular signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the additio...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(97)00036-3
更新日期：1998-03-01 00:00:00
abstract：:Measurements of prostaglandin E2 (PGE2)-induced adenylyl cyclase activity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE2 (less than 10 mM) and stimulation at higher concentrations. This biphasic effect of PGE2 was obtained when adenylyl cyclase...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(92)90073-h
更新日期：1992-05-01 00:00:00
abstract：:Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ectopic F(1)-ATPase stimulates the production of extracellular ADP that activates a P2Y(13...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.09.016
更新日期：2009-01-01 00:00:00
abstract：:Neuroprotective effects of alpha(2)-adrenergic receptor (AR) agonists are mediated via the alpha(2A)AR subtype, but the molecular mechanisms underlying these actions are still not elucidated. A two-hybrid screen was performed to identify new proteins that may control alpha(2)AR receptor function and trafficking. This ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.05.011
更新日期：2009-10-01 00:00:00
